Extended Infusion of Piperacillin/Tazobactam Found to Lower Mortality, Incidence of C. Difficile Infection

Implementing extended infusion of piperacillin/tazobactam (TZP) in the hospital setting was found to reduce the risk of 14-day mortality and the incidence of C. difficile infection (CDI), according to a study published in Infectious Medicine.

The study authors compared the clinical, safety, and economic outcomes of patients administered extended infusion with TZP with standard infusion and TZP. Prior research indicates that extended infusion TZP produces improved clinical outcomes vs standard infusion treatment, according to the authors of the current study. They added that data are lacking in evaluating these options for non-critically ill patients.

They noted that gram-negative infections are associated with significant morbidity and mortality among hospitalized patients and resistant organisms have outpaced the development of new antibiotics. Hospital-wide extended infusion TZP therapy was implemented in 2012.

“One way to optimize the use of current antimicrobials is to apply innovative pharmacokinetic/pharmacodynamic (PK/PD) dosing strategies to improve clinical outcomes,” the authors wrote. “(TZP) exhibits time-dependent killing, with a PK/PD goal of time above minimum inhibitory concentration (MIC) of 50%–60% correlating with its bactericidal effect.”

The retrospective cohort study evaluated all adult patients administered extended infusion TZP 3.375 g intravenous q8h infusion over 4 hours (n = 2034) and standard infusion TZP (n = 1634) for at least 48 hours over the course of 3 years. The study authors looked to evaluate the primary outcomes of 14-day mortality.

They also examined various secondary outcomes, such as length of hospital stay, nursing plus pharmacy cost, occurrence of CDI, readmission within 30 days, and change in P aeruginosa minimum inhibitory concentration (MIC) distribution for the treatment.

The study authors incorporated a logistic regression model to evaluate the primary and secondary outcomes and analyzed length of stay using time to event analysis. Extended infusion was associated with reduced odds of mortality (odds ratio [OR], 0.76; 95% confidence interval [CI], 0.63-0.91), reduced odds of CDI (OR, 0.59; 95% CI, 0.41-0.84), and an 8% lower cost (estimate 0.92, 95% CI 0.87-0.98) vs the standard infusion.

“Overall, extended infusion piperacillin/tazobactam was associated with lower odds of 14-day mortality compared to standard infusion piperacillin/tazobactam,” the study authors wrote. “Other factors that increased the odds of death included older age, higher Charlson Score, being male and being in ICU at the start of TZP therapy.”

The data also show the standard infusion cohort had more patients with P aeruginosa isolates from blood and respiratory cultures, ICU status at the start of therapy, and longer duration of treatment. For the unadjusted outcomes, the extended infusion cohort had fewer patients who died within 14 days, shorter length of stay, reduced incidence of CDI, lower nursing costs, and lower total costs.

There was no difference observed in length of stay or readmission within 30 days between the 2 treatment cohorts, however.

“In conclusion, our study showed extended infusion piperacillin/tazobactam to be associated with a lower risk of 14-day mortality, lower incidence of C. difficile infections and lower costs,” the study authors wrote. “However, future studies should use the current recommended dosing of 4.5 g IV q8h infused over 4 hours to optimize achievement of PK/PD goals and to expand on clinical evidence in this area.”

Reference

April J. Chan, Gerald Lebovic, Michael Wan, Yan Chen, Elizabeth Leung, Bradley J. Langford, Jenny Seah, Linda R. Taggart, Mark Downing. Impact of extended-infusion piperacillin-tazobactam in a Canadian community hospital. Infectious Medicine, 2023, ISSN 2772-431X, https://doi.org/10.1016/j.imj.2023.01.005. https://www.sciencedirect.com/science/article/pii/S2772431X23000059.